目的 以中醫(yī)“異病同治”理論為依據(jù)，采用網(wǎng)絡藥理學與分子對接方法探討化肝煎“異病同治”失眠、慢性萎縮性胃炎和胃食管反流病的作用靶點及可能作用機制。方法 通過中藥系統(tǒng)藥理學數(shù)據(jù)庫與分析平臺（TCMSP）等中藥化合物數(shù)據(jù)庫結合文獻挖掘獲取化肝煎的化學成分和作用靶點；結合GeneCards、OMIM、PharmGKB、DRUGBANK、TTD數(shù)據(jù)庫獲取化肝煎治療失眠、慢性萎縮性胃炎和胃食管反流病的作用靶點。采用Cytoscape軟件繪制化肝煎中藥-成分-靶點網(wǎng)絡，利用Venny軟件得出相關交集基因?；贑ytoscape軟件繪制化肝煎-成分-靶點可視化網(wǎng)絡圖，借助STRING數(shù)據(jù)庫及Cytoscape軟件構建蛋白質相互作用（PPI）網(wǎng)絡，分析獲得核心作用靶點。采用Metascape平臺工具對其進行基因本體論（GO）注釋及京都基因與基因組百科全書（KEGG）通路富集分析。使用AutodockTools軟件對化肝煎主要活性成分與疾病作用靶點進行分子對接。結果 篩選得到化肝煎化學成分56個，疾病靶點：失眠438個，慢性萎縮性胃炎868個，胃食管反流病4 252個，以及20個藥物成分和疾病共同靶點。PPI網(wǎng)絡中關鍵蛋白排名靠前的靶點為IL6、NCF1、PTGS2、CRP、MPO、PPARG、TNF等。獲得GO富集分析結果排名靠前的有452種生物過程（BP）、19種分子功能（MF）、6種細胞組分（CC），KEGG信號通路主要有6條信號通路。分子對接結果顯示關鍵成分與對應靶點具有較好的結合活性。結論 化肝煎治療失眠、慢性萎縮性胃炎和胃食管反流病可能涉及TNF、IL6、PTGS2、PPARG、CRP等為代表的核心靶點，其實現(xiàn)異病同治的作用可能與脂質信號通路調控炎癥、細胞因子反應等有關。

Objective Based on the theory of "treating the different diseases with the same therapy" in traditional Chinese medicine, network pharmacology and molecular docking method were used to explore the target and possible mechanism of Hua-Gan Decoction (HGD) "treating the different diseases with the same therapy" in insomnia, chronic atrophic gastritis and gastroesophageal reflux disease. Methods The chemical constituents and action targets of HGD were obtained by TCMSP and literature mining. Combined with GeneCards, OMIM, PharmGKB, DRUGBANK and TTD database, the therapeutic targets of HGD for insomnia, chronic atrophic gastritis and gastroesophageal reflux disease were obtained. Cytoscape software was used to draw the "TCMcomponent-target" network of gain, and the related intersection genes were obtained by Venny software. Based on Cytoscape software, a visual network map of "HGD-component-target" was drawn, and a PPI network was constructed with the help of STRING database and Cytoscape software to analyze and obtain the core targets. The Metascape platform tool was used for GO enrichment analysis and KEGG pathway analysis. AutodockTools were used to conduct molecular docking between the main active ingredients of HGD and the disease targets. Results A total of 56 chemical components of HGD, 438 disease targets of insomnia, 868 chronic atrophic gastritis, 4 252 gastroesophageal reflux disease and 20 common targets of drug components and diseases were screened. The top targets of key proteins in PPI network were IL6, NCF1, PTGS2, CRP, MPO, PPARG, TNF, etc. GO enrichment analysis results were obtained for 452 biological processes, 19 molecular functions and six cellular components, and KEGG signaling pathways mainly included six signaling pathways. The molecular docking results showed that the key components had good binding activity with corresponding targets. Conclusion HGD may involve the core targets represented by TNF, IL6, PTGS2,PPARG and CRP in the treatment of insomnia, chronic atrophic gastritis and gastroesophageal reflux disease, and its effect on the simultaneous treatment of different diseases may be related to the regulation of lipid signaling pathway in inflammation and cytokine response.

R285.5

國家重點研發(fā)計劃項目（2017YFC1700601）；"十三五"國家重點研發(fā)計劃中醫(yī)藥現(xiàn)代化研究專項（2017YFC1703703）；陜西省特支計劃科技創(chuàng)新領軍人才項目（646）